A physiologically based mathematical model of integrated calcium homeostasis and bone remodeling

• Published in: Bone (New York, N.Y.) Vol. 46; no. 1; pp. 49 - 63
• Main Authors: Peterson, Mark C, Riggs, Matthew M
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.01.2010; Elsevier
• Subjects: Biological and medical sciences; Bone remodeling; Bone Remodeling - physiology; Calcitriol - metabolism; Calcium - metabolism; Endocrine regulation of calcium and bone; Fundamental and applied biological sciences. Psychology; Models, Biological; Models, Theoretical; Orthopedics; Parathyroid hormone; Parathyroid Hormone - blood; Phosphates - metabolism; RANK–RANKL–OPG; Skeleton and joints; Systems biology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: osteoarticular system, musculoskeletal system; RANKL; Endocrine regulation of calcium and bone; PTH; transforming growth factor beta; OPG; once daily; RANK; Bone remodeling; bone mineral density; NF-κB; GFR; QD; 1-α-OH; PO4; receptor activator of NF-κB ligand; BMD; TGF-β; RK4; receptor activator of NF-κB; parathyroid hormone; calcium; ROB; glomerular filtration rate; extracellular fluid; phosphate; ECF; nuclear factor-kappa B; RANK–RANKL–OPG; 1-alpha hydroxylase; BMU; bone morphogenic unit; Systems biology; responding osteoblast; fourth-order Runge–Kutta algorithm; osteoprotegerin; Ca; Parathyroid hormone; Calcium; Receptor activator Nfkb ligand; Morphology; Homeostasis; Biology; Bone; Mathematical model; RANK-RANKL-OPG
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2009.08.053

Abstract Bone biology is physiologically complex and intimately linked to calcium homeostasis. The literature provides a wealth of qualitative and/or quantitative descriptions of cellular mechanisms, bone dynamics, associated organ dynamics, related disease sequela, and results of therapeutic interventions. We present a physiologically based mathematical model of integrated calcium homeostasis and bone biology constructed from literature data. The model includes relevant cellular aspects with major controlling mechanisms for bone remodeling and calcium homeostasis and appropriately describes a broad range of clinical and therapeutic conditions. These include changes in plasma parathyroid hormone (PTH), calcitriol, calcium and phosphate (PO4), and bone-remodeling markers as manifested by hypoparathyroidism and hyperparathyroidism, renal insufficiency, daily PTH 1–34 administration, and receptor activator of NF-κB ligand (RANKL) inhibition. This model highlights the utility of systems approaches to physiologic modeling in the bone field. The presented bone and calcium homeostasis model provides an integrated mathematical construct to conduct hypothesis testing of influential system aspects, to visualize elements of this complex endocrine system, and to continue to build upon iteratively with the results of ongoing scientific research.